Acid-sensing ion channel 3 - Rattus norvegicus (Rat)

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O35240 (ASIC3_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 92. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Acid-sensing ion channel 3
Short name=ASIC3

Alternative name(s):
Amiloride-sensitive cation channel 3
Dorsal root ASIC
Short name=DRASIC

Gene names

Name:	Asic3
Synonyms:	Accn3, Drasic

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	533 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Generates a biphasic current with a fast inactivating and a slow sustained phase. In sensory neurons is proposed to mediate the pain induced by acidosis that occurs in ischemic, damaged or inflamed tissue. May be involved in hyperalgesia. May play a role in mechanoreception. Heteromeric channel assembly seems to modulate channel properties. Ref.7 Ref.9 Ref.14
Subunit structure	Homotrimer or heterotrimer with other ASIC proteins By similarity. Interacts with STOM, LIN7B, MAGI1 and GOPC By similarity. Interacts with DLG4 and ASIC2. Ref.2 Ref.17
Subcellular location	Cytoplasm By similarity. Cell membrane; Multi-pass membrane protein By similarity. Note: In part cytoplasmic in cochlea cells By similarity. Cell surface expression may be stabilized by interaction with LIN7B and cytoplasmic retention by interaction with DLG4. Ref.11 Ref.17
Tissue specificity	Expressed in sciatic nerve and dorsal root ganglion (at protein level). Expressed in sensory neurons of dorsal root ganglion. Expressed in Golgi interneurons in the granular layer. Also found in superior cervical ganglia, spinal chord and brain stem. Ref.1 Ref.3 Ref.5 Ref.11
Developmental stage	Expression is first detected at E15.5. Strongly expressed perinatally. Ref.12
Induction	Transcriptionally regulated by the proinflamatory mediators nerve growth factor, serotonin, interleukin-1 and bradykinin. Up-regulation upon tissues inflammation is abolished by anti-inflammatory drugs. Ref.6 Ref.7 Ref.8 Ref.10 Ref.12 Ref.13
Domain	The PDZ domain-binding motif is involved in interaction with LIN7A, GOPC and MAGI1/BAIAP1 By similarity.
Post-translational modification	Phosphorylated by PKA By similarity. Phosphorylated by PKC. In vitro, PRKCABP/PICK-1 is necessary for PKC phosphorylation and activation of a ASIC3/ACCN3-ASIC2/ASIC2b channel, but does not activate a homomeric ASIC3/ACCN3 channel. Ref.16
Miscellaneous	Potentiated by FMRFamide-related neuropeptides By similarity. Sensitized and potentiated by NPFF and NPSF. Regulated by lactate and Ca²⁺. Specifically inhibited by APETx2, a sea anemone toxin. Inhibited by anti-inflammatory drugs like salicylic acid.
Sequence similarities	Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC3 subfamily. [View classification]

Ontologies

Keywords
Biological process	Ion transport Sodium transport Transport
Cellular component	Cell membrane Cytoplasm Membrane
Domain	Transmembrane Transmembrane helix
Ligand	Sodium
Molecular function	Ion channel Sodium channel
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	detection of chemical stimulus involved in sensory perception of pain Inferred from electronic annotation. Source: Compara detection of mechanical stimulus involved in sensory perception of pain Inferred from electronic annotation. Source: Compara detection of temperature stimulus involved in sensory perception of pain Inferred from electronic annotation. Source: Compara response to acid Inferred from direct assay Ref.1. Source: MGI response to heat Inferred from electronic annotation. Source: Compara
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Inferred from direct assay Ref.1. Source: MGI
Molecular_function	PDZ domain binding Inferred from mutant phenotype PubMed 16234233. Source: RGD enterobactin transporter activity Inferred from electronic annotation. Source: Compara ligand-gated sodium channel activity Inferred from direct assay Ref.1. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Slc9a3r1	Q9JJ19	5	EBI-982374,EBI-982391
Slc9a3r2	Q920G2	2	EBI-982374,EBI-982439

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 533

533

Acid-sensing ion channel 3

PRO_0000181303

Regions

Topological domain

1 – 19

Cytoplasmic Potential

Transmembrane

20 – 40

Helical; Potential

Topological domain

41 – 435

395

Extracellular Potential

Transmembrane

436 – 456

Helical; Potential

Topological domain

457 – 533

Cytoplasmic Potential

Motif

530 – 533

PDZ-binding By similarity

Sites

Site

Potassium ion selectivity and permeability

Amino acid modifications

Modified residue

Phosphothreonine; by PKC Probable

Modified residue

523

Phosphoserine; by PKC Probable

Glycosylation

176

N-linked (GlcNAc...) Potential

Glycosylation

400

N-linked (GlcNAc...) Potential

Disulfide bond

93 ↔ 187

By similarity

Disulfide bond

165 ↔ 172

By similarity

Disulfide bond

283 ↔ 372

By similarity

Disulfide bond

317 ↔ 368

By similarity

Disulfide bond

321 ↔ 366

By similarity

Disulfide bond

330 ↔ 352

By similarity

Disulfide bond

332 ↔ 344

By similarity

Experimental info

Mutagenesis

V → P: No effect on selectivity or channel function. Ref.4

Mutagenesis

F → S: Loss of channel function. Ref.4

Mutagenesis

T → K: Alters selectivity of the channel for sodium. No effect on channel function. Ref.4

Mutagenesis

T → G: Loss of regulation by PKC through PRKCABP; when associated with G-523. Ref.16

Mutagenesis

523

S → G: Loss of regulation by PKC through PRKCABP; when associated with G-40. Ref.16

Sequences

Sequence

Length

Mass (Da)

Tools

O35240 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 294B57322C74B3DC
Show »

FASTA

533

59,227

        10         20         30         40         50         60 
MKPRSGLEEA QRRQASDIRV FASSCTMHGL GHIFGPGGLT LRRGLWATAV LLSLAAFLYQ 

        70         80         90        100        110        120 
VAERVRYYGE FHHKTTLDER ESHQLTFPAV TLCNINPLRR SRLTPNDLHW AGTALLGLDP 

       130        140        150        160        170        180 
AEHAAYLRAL GQPPAPPGFM PSPTFDMAQL YARAGHSLED MLLDCRYRGQ PCGPENFTVI 

       190        200        210        220        230        240 
FTRMGQCYTF NSGAHGAELL TTPKGGAGNG LEIMLDVQQE EYLPIWKDME ETPFEVGIRV 

       250        260        270        280        290        300 
QIHSQDEPPA IDQLGFGAAP GHQTFVSCQQ QQLSFLPPPW GDCNTASLDP DDFDPEPSDP 

       310        320        330        340        350        360 
LGSPRPRPSP PYSLIGCRLA CESRYVARKC GCRMMHMPGN SPVCSPQQYK DCASPALDAM 

       370        380        390        400        410        420 
LRKDTCVCPN PCATTRYAKE LSMVRIPSRA SARYLARKYN RSESYITENV LVLDIFFEAL 

       430        440        450        460        470        480 
NYEAVEQKAA YEVSELLGDI GGQMGLFIGA SLLTILEILD YLCEVFQDRV LGYFWNRRSA 

       490        500        510        520        530 
QKRSGNTLLQ EELNGHRTHV PHLSLGPRPP TTPCAVTKTL SASHRTCYLV TRL

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References

[1]	"Molecular cloning of a non-inactivating proton-gated Na+ channel specific for sensory neurons." Waldmann R., Bassilana F., de Weille J.R., Champigny G., Heurteaux C., Lazdunski M. J. Biol. Chem. 272:20975-20978(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[2]	"A modulatory subunit of acid sensing ion channels in brain and dorsal root ganglion cells." Lingueglia E., de Weille J.R., Bassilana F., Heurteaux C., Sakai H., Waldmann R., Lazdunski M. J. Biol. Chem. 272:29778-29783(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ASIC1. Strain: Wistar. Tissue: Brain.
[3]	"A sensory neuron-specific, proton-gated ion channel." Chen C.-C., England S., Akopian A.N., Wood J.N. Proc. Natl. Acad. Sci. U.S.A. 95:10240-10245(1998) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[4]	"The pre-transmembrane 1 domain of acid-sensing ion channels participates in the ion pore." Coscoy S., de Weille J.R., Lingueglia E., Lazdunski M. J. Biol. Chem. 274:10129-10132(1999) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF VAL-20; PHE-21 AND THR-26.
[5]	"Mammalian ASIC2a and ASIC3 subunits co-assemble into heteromeric proton-gated channels sensitive to Gd3+." Babinski K., Catarsi S., Biagini G., Seguela P. J. Biol. Chem. 275:28519-28525(2000) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[6]	"Nonsteroid anti-inflammatory drugs inhibit both the activity and the inflammation-induced expression of acid-sensing ion channels in nociceptors." Voilley N., de Weille J.R., Mamet J., Lazdunski M. J. Neurosci. 21:8026-8033(2001) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION, INHIBITION BY DRUGS.
[7]	"Lactate enhances the acid-sensing Na+ channel on ischemia-sensing neurons." Immke D.C., McCleskey E.W. Nat. Neurosci. 4:869-870(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REGULATION BY LACTATE, FUNCTION.
[8]	"Selective modulation of heteromeric ASIC proton-gated channels by neuropeptide FF." Catarsi S., Babinski K., Seguela P. Neuropharmacology 41:592-600(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REGULATION BY NPFF.
[9]	"Acid-sensing ion channel 3 matches the acid-gated current in cardiac ischemia-sensing neurons." Sutherland S.P., Benson C.J., Adelman J.P., McCleskey E.W. Proc. Natl. Acad. Sci. U.S.A. 98:711-716(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Proinflammatory mediators, stimulators of sensory neuron excitability via the expression of acid-sensing ion channels." Mamet J., Baron A., Lazdunski M., Voilley N. J. Neurosci. 22:10662-10670(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[11]	"Functional implications of the localization and activity of acid-sensitive channels in rat peripheral nervous system." Alvarez de la Rosa D., Zhang P., Shao D., White F., Canessa C.M. Proc. Natl. Acad. Sci. U.S.A. 99:2326-2331(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[12]	"How nerve growth factor drives physiological and inflammatory expressions of acid-sensing ion channel 3 in sensory neurons." Mamet J., Lazdunski M., Voilley N. J. Biol. Chem. 278:48907-48913(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE, INDUCTION BY NGFB.
[13]	"Protons open acid-sensing ion channels by catalyzing relief of Ca2+ blockade." Immke D.C., McCleskey E.W. Neuron 37:75-84(2003) [PubMed] [Europe PMC] [Abstract] Cited for: REGULATION BY LACTATE AND CALCIUM.
[14]	"Effects of neuropeptide SF and related peptides on acid sensing ion channel 3 and sensory neuron excitability." Deval E., Baron A., Lingueglia E., Mazarguil H., Zajac J.-M., Lazdunski M. Neuropharmacology 44:662-671(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	"A new sea anemone peptide, APETx2, inhibits ASIC3, a major acid-sensitive channel in sensory neurons." Diochot S., Baron A., Rash L.D., Deval E., Escoubas P., Scarzello S., Salinas M., Lazdunski M. EMBO J. 23:1516-1525(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INHIBITION BY APETX2 TOXIN.
[16]	"ASIC2b-dependent regulation of ASIC3, an essential acid-sensing ion channel subunit in sensory neurons via the partner protein PICK-1." Deval E., Salinas M., Baron A., Lingueglia E., Lazdunski M. J. Biol. Chem. 279:19531-19539(2004) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF THR-40 AND SER-523, PHOSPHORYLATION AT THR-40 AND SER-523.
[17]	"PSD-95 and Lin-7b interact with acid-sensing ion channel-3 and have opposite effects on H+- gated current." Hruska-Hageman A.M., Benson C.J., Leonard A.S., Price M.P., Welsh M.J. J. Biol. Chem. 279:46962-46968(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DLG4, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF013598 mRNA. Translation: AAB69328.1.
IPI	IPI00207274.
RefSeq	NP_775158.1. NM_173135.1.
UniGene	Rn.24225.
3D structure databases
ProteinModelPortal	O35240.
SMR	O35240. Positions 41-464.
ModBase	Search...
Protein-protein interaction databases
IntAct	O35240. 2 interactions.
MINT	MINT-1777886.
STRING	10116.ENSRNOP00000011300.
Protein family/group databases
TCDB	1.A.6.1.2. epithelial Na+ channel (ENaC) family.
PTM databases
PhosphoSite	O35240.
Proteomic databases
PRIDE	O35240.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000011300; ENSRNOP00000011300; ENSRNOG00000008380.
GeneID	286920.
KEGG	rno:286920.
Organism-specific databases
CTD	9311.
RGD	708578. Asic3.
Phylogenomic databases
eggNOG	NOG262945.
GeneTree	ENSGT00640000091217.
HOGENOM	HOG000247010.
HOVERGEN	HBG004150.
InParanoid	O35240.
KO	K04830.
OMA	TECHMEC.
OrthoDB	EOG4NP737.
Gene expression databases
ArrayExpress	O35240.
Genevestigator	O35240.
GermOnline	ENSRNOG00000008380. Rattus norvegicus.
Family and domain databases
InterPro	IPR004724. EnaC. IPR001873. Na+channel_ASC. IPR020903. Na+channel_ASC_CS. [Graphical view]
PANTHER	PTHR11690. PTHR11690. 1 hit.
Pfam	PF00858. ASC. 1 hit. [Graphical view]
PRINTS	PR01078. AMINACHANNEL.
TIGRFAMs	TIGR00859. ENaC. 1 hit.
PROSITE	PS01206. ASC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O35240.
ChEMBL	CHEMBL5757.
NextBio	625060.

Entry information

Entry name

ASIC3_RAT

Accession

Primary (citable) accession number: O35240

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 13, 2005
Last sequence update:	January 1, 1998
Last modified:	May 1, 2013
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents